Abstract
Background & Aim Dendritic cells (DCs) have been implicated in the pathogenesis of type 1 diabetes mellitus (T1DM) and have potential as immunotherapeutic agents. The inhibition of DCs profile and function is part of the multi-level immunomodulatory properties displayed by human Mesenchymal Stem Cells (MSCs). Due to their potent immunoregulatory and immunomodulatory functions, MSCs have emerged as a therapeutic regimen in the management of many diseases that have no effective treatment, including T1DM. It has been shown that in T1DM patients DCs respond in terms of maturation, activation, and phenotype when co-cultured with autologous and allogeneic Bone Marrow derived MSCs (BM-MSC). In the recent study, the effect of autologous BM-MSCs in comparison with the allogeneic BM-MSCs co-cultured with monocyte-derived DCs isolated from TIDM patients was investigated for the first time. Methods, Results & Conclusion Methods Autologous and allogeneic BM-MSCs were isolated from healthy donors and T1DM patients. Then, morphology and surface markers expression were analyzed. Mature DCs (mDCs) were differentiated from CD14+ cells, obtained from newly diagnosed T1DM patients, pulsed with antigen Glutamic Acid Decarboxylase (GAD65) and co-cultured with BM-MSCs. the expression of co-stimulatory molecules and maturation markers were evaluated by flow cytometery. The level of anti-inflammatory cytokines was measured by ELISA. Autologous CD14- cells and GAD65 pulsed mDCs were co-cultured and IFN-γ ELISPOT responses were performed. Secreted level of IL-17 was measured Result autologous and allogeneic BM-MSCs have a comparable effect on GAD65 pulsed mature mDCs in terms of phenotype and maturation marker expression. Interestingly, the secretion levels of (IL-10, IL-6 and TGF-B) increased significantly in the allogeneic BM-MSCs when co-cultured with GAD65 pulsed mDCs. GAD65 pulsed-mDCs/T-cells showed decreased IFN-γ production when co-cultured with BM-MSCs. Moreover, the level of IL-17 secretion declined significantly in the allogeneic BM-MSCs compared to the autologous cells. Conclusion This research demonstrated in vitro the potent immunomodulatory effect of allogeneic BM-MSCs on pancreatic islet antigen specific T-Cells in newly-diagnosed T1DM patients through the induction of DCs’ tolerogenic function. These DCs can contribute to the suppressing T-cell mediated immunity and the promotion of anti-inflammatory responses exerted by BM-MSCs.
Published Version
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a call